Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prev...Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prevalence of good anticoagulation in patients treated with VKA in Lomé and describe associated factors. Methods: This was a cross-sectional study conducted from November 2019 to October 2020 in the cardiology departments of two University teaching hospitals in Lomé (CHU Sylvanus Olympio and CHU Campus), involving patients on VKA for ≥3 months, with a target international normalized ratio (INR) of 2.5 and a therapeutic margin between 2 and 3. The quality of anticoagulation was assessed by the time in therapeutic range (TTR) which was assessed by the Rosendaal method. Good anticoagulation was defined by a TTR > 70%. Results: A total of 344 patients were included (mean age = 58 ± 13.8 years, women = 56.1%). Indications for VKA treatment were represented by venous thromboembolic disease (43.3%), supraventricular arrhythmia (28.2%), severe left ventricular systolic dysfunction (19.8%) and pulmonary hypertension (8.7%). The average TTR was 47.6 ± 20.8%. The rate of good anticoagulation was 17.7%. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol (OR = 11.17;95% CI: 3.2 - 39.6;p = 0.0002), concomitant low-dose aspirin (OR 4.44;95% CI: 1.4 - 13.9;p = 0.01) and INR monitoring exclusively by the patient himself (OR = 4.92;95% CI: 1.5 - 16.3;p = 0.008). The rate of thromboembolic and hemorrhagic complications was each 2.6% and was not correlated with the quality of anticoagulation. Quality of anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol, concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. Conclusion: The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKA dose, and the use of prescription assistance software.展开更多
Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improv...Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.展开更多
Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in ...Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.展开更多
Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of est...Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of estrogen pre-treatment in antagonist prorocol were searched in PubMed,Web of Science,China National Knowledge Infrastructure,Wanfang Database.R software was used for meta-analysis.Results:Seven RCTs and two retrospective studies were included.In order to explore the source of heterogeneity,subgroup analysis was used,which was mainly conducted according to the ovarian response of the included population,which were divided into low responders,non-low responders and mixed responders.In the study about gonadotropin hormone(Gn)days,patients were divided into wash-out subgroup and non-wash-out subgroup according to drug use-pattern.Meta-results showed that the number of Gn days increased significantly in the non-wash-out subgroup(WMD=1.07,95%CI[0.83;1.31],I2=66%).The number of Gn days in the wash-out subgroup were not affected(WMD=-0.12,95%CI[-0.45;0.21],I2=0%).In the low-response subgroup,the number of oocytes retrieved(WMD=0.46,95%CI[-0.23;1.16],I2=81%),the fresh cycle clinical pregnancy rate(RR=0.77,95%CI[0.55;1.06],I2=73%)and the cycle cancellation rate(RR=0.80,95%CI[0.40;1.61],I2=83%)were not significantly changed with estrogen pre-treatment.In the non-low-response subgroup,the number of oocytes obtained(WMD=0.21,95%CI[-0.69;1.11],I2=2%),fresh cycle clinical pregnancy rate(RR=0.94,95%CI[0.77;1.14],I2=41%),live birth rate(RR=0.82,95%CI[0.62;1.08],I2=0%)and cycle cancellation rate(RR=0.89,95%CI[0.54;1.47],I2=2%)were not significantly changed with estrogen pre-treatment.Conclusions:Estrogen pre-treatment(with non-wash-out period)in antagonist protocol increases Gn days,dose not improve IVF outcomes in non-low responders and low responders.展开更多
BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-li...BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.展开更多
Aflatoxin is a strong carcinogenic and toxic fungal toxin produced by Aspergillus flavus and other Aspergillus species,and can seriously threaten the health of consumers,thus becoming a global concern.Corn,as an impor...Aflatoxin is a strong carcinogenic and toxic fungal toxin produced by Aspergillus flavus and other Aspergillus species,and can seriously threaten the health of consumers,thus becoming a global concern.Corn,as an important oil and economic crop,is highly susceptible contaminated by aflatoxin.In this study,antagonistic bacteria with strong inhibitory effect on aflatoxin were screened to provide support for the treatment aflatoxin contamination control in corn.Ten strains which have strong antagonistic effects against A.flavus were isolated from healthy corn from different corn producing areas in China.Among them,the antagonistic bacteria JTFM1001 through corn kernels in vivo and field experiment,the inhibition effect of aflatoxin contamination reached above 70%and 55%,respectively.And the strain was identified as Bacillus subtilis based on its morphological,physiological and biochemical characteristics and phylogenetic analysis of 16S rDNA.In addition,our data showed that it can colonize in the rhizosphere and survive for a long time,forming the dominant flora,with broad application prospect.Finally,we were surprised to find that the antibacterial metabolites secreted by the antagonistic bacteria was one of the mechanisms of its inhibition of A.flavus and aflatoxin.This will provide us with new ideas and perspectives on the effective prevention and control of aflatoxin contamination in corn and corn oil.展开更多
Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each g...Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.展开更多
AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND...AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.展开更多
BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma...BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.展开更多
AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLIN...AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.展开更多
AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs ...AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.展开更多
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) ...Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.展开更多
Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC...Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.展开更多
AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine ...AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.展开更多
This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger p...This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.展开更多
Objective: To investigate the effects of Andrographis paniculata(Burm.f.) Wall. Ex Nees(A. paniculata) on expressions and activities of catalase, superoxide dismutase and alkylhydroperoxide reductase C in Staphylococc...Objective: To investigate the effects of Andrographis paniculata(Burm.f.) Wall. Ex Nees(A. paniculata) on expressions and activities of catalase, superoxide dismutase and alkylhydroperoxide reductase C in Staphylococcus aureus(S. aureus) with respect to its survival in vitro. Methods: Antioxidative property of methanolic leaves extract of A. paniculata(0.06 mg/m L). Minimum inhibitory concentration(MIC) was determined by its ability to reduce hydrogen peroxide(H_2O_2) toxicity against S. aureus ATCC 25923(3.8×10~8 cfu/m L). Effects of the extract on expressions of kat A(encoding catalase), sod A and sod M [encoding superoxide dismutases(SODs)], and ahp C [encoding alkylhydroperoxide reductase C(AhpC)] in S. aureuswere determined by RT-q PCR and corresponding enzyme activity assays were performed. Nitroblue tetrazolium reduction(NBT) assay was performed to determine effects of the extract on intracellular and extracellular levels of O_2-in S. aureus. Results: Cells challenged with 7.5 mmol/L H_2O_2 showed 0% survival in 30 min whereas 25% survived after treatment with the extract and H_2O_2. Cells that were treated with the extract alone had 43% survival in the same exposure period. Expressions of sod A and sod M genes in extract-treated cells were lowered 0.8-fold and 0.7-fold, respectively with decrease in total SOD activity of 26.8 U compared to untreated cells, 32.4 U(P<0.05). In contrast, extract-treated S. aureus cells showed 3.3-fold increase in kat A expression with corresponding increase in catalase activity of 1.828 U compared to untreated cells which was 1.248 U,(P<0.05). More profoundly, ahp C expression was increased 61-fold in extract-treated cells,(P<0.05) with corresponding increase in Ahp C activity of 0.018 U compared to untreated cells, 0.012U,(P<0.05). Extract-treated cells had significantly lower intra-and extracellular O_2-levels with absorbance readings(A_(575nm)) of 0.340 and 0.524 compared to untreated cells which were 0.516 and 0.928(P<0.05), respectively. Conclusions: Taken together these results suggest that the low MIC of A. paniculatamethanolic leaves extract(0.06 mg/m L) reduce H_2O_2 toxicity and more importantly, was in itself effectively inhibitory against S. aureus. Further, our observations suggest that a probable mode of its inhibitory mechanism against S. aureus is by reducing total SOD activity through downregulation of sod A and sod M expressions.展开更多
At present, the studies on multi-team antagonistic games(MTAGs) are still in the early stage, because this complicated problem involves not only incompleteness of information and conflict of interests, but also select...At present, the studies on multi-team antagonistic games(MTAGs) are still in the early stage, because this complicated problem involves not only incompleteness of information and conflict of interests, but also selection of antagonistic targets.Therefore, based on the previous researches, a new framework is proposed in this paper, which is dynamic multi-team antagonistic games with incomplete information(DMTAGII) model.For this model, the corresponding concept of perfect Bayesian Nash equilibrium(PBNE) is established and the existence of PBNE is also proved. Besides, an interactive iteration algorithm is introduced according to the idea of the best response for solving the equilibrium. Then, the scenario of multiple unmanned aerial vehicles(UAVs) against multiple military targets is studied to solve the problems of tactical decision making based on the DMTAGII model. In the process of modeling, the specific expressions of strategy, status and payoff functions of the games are considered, and the strategy is coded to match the structure of genetic algorithm so that the PBNE can be solved by combining the genetic algorithm and the interactive iteration algorithm.Finally, through the simulation the feasibility and effectiveness of the DMTAGII model are verified. Meanwhile, the calculated equilibrium strategies are also found to be realistic, which can provide certain references for improving the autonomous ability of UAV systems.展开更多
Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric cancers.To date,16 cases of PIVKA-...Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric cancers.To date,16 cases of PIVKA-Ⅱ-producing gastric cancer have been reported,2 of which were reported by us and all of which were identified in Japan.There are no symptoms specific to PIVKA-Ⅱ-producing gastric cancer,and the representative clinical symptoms are general fatigue,appetite loss,and upper abdominal pain.Serum alpha-feto-protein(AFP)levels are also increased in almost allcases.Liver metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is ob-served in approximately 20% of cases.Differential diagnosis between metastatic liver tumor and HCC is often difficult.Grossly,almost all cases appear as advanced gastric cancer.Histologically,a hepatoid pattern is observed in many cases,in addition to a moderately to poorly differentiated adenocarcinoma component.The production of PIVKA-Ⅱ and AFP is usually confirmed using immunohistochemical staining.Treatment and prognosis largely depends on the existence of liver meta-stasis,and the prognosis of patients with liver metas-tasis is very poor.PIVKA-Ⅱ may be produced during the hepatocellular metaplasia of the tumor cells.展开更多
To explore the metabolic responses of marine-derived Trichoderma fungi to environmental stresses, the survivability, metabolism, and antagonism of ten marine isolates have been examined. Their survival in both freshwa...To explore the metabolic responses of marine-derived Trichoderma fungi to environmental stresses, the survivability, metabolism, and antagonism of ten marine isolates have been examined. Their survival in both freshwater and seawater indicates them to be facultative marine fungi, but they are more adaptable to marine environment. Most of them feature strain-specific and positive metabolic responses to seawater, which also usually result in the higher proportions of heteroatom-bearing and unsaturated units in mycelial constituents. Seawater factors can promote many strains to produce bioactive metabolites, including plant pathogen- and marine phytoplankton-inhibitory and marine animal-toxic ones, but the eff ects of NaCl are often weak or negative. The inhibition of marine phytoplankton corresponds to the intracellular accumulation of heteroatom-bearing and unsaturated units under seawater condition, and the varied toxicities to marine animals further signify the divergences of lipophilic exudates under diff erent conditions. The results may contribute to further understanding and mining the structural diversity and biological activity of secondary metabolites from marine-derived Trichoderma fungi.展开更多
Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previou...Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.展开更多
文摘Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prevalence of good anticoagulation in patients treated with VKA in Lomé and describe associated factors. Methods: This was a cross-sectional study conducted from November 2019 to October 2020 in the cardiology departments of two University teaching hospitals in Lomé (CHU Sylvanus Olympio and CHU Campus), involving patients on VKA for ≥3 months, with a target international normalized ratio (INR) of 2.5 and a therapeutic margin between 2 and 3. The quality of anticoagulation was assessed by the time in therapeutic range (TTR) which was assessed by the Rosendaal method. Good anticoagulation was defined by a TTR > 70%. Results: A total of 344 patients were included (mean age = 58 ± 13.8 years, women = 56.1%). Indications for VKA treatment were represented by venous thromboembolic disease (43.3%), supraventricular arrhythmia (28.2%), severe left ventricular systolic dysfunction (19.8%) and pulmonary hypertension (8.7%). The average TTR was 47.6 ± 20.8%. The rate of good anticoagulation was 17.7%. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol (OR = 11.17;95% CI: 3.2 - 39.6;p = 0.0002), concomitant low-dose aspirin (OR 4.44;95% CI: 1.4 - 13.9;p = 0.01) and INR monitoring exclusively by the patient himself (OR = 4.92;95% CI: 1.5 - 16.3;p = 0.008). The rate of thromboembolic and hemorrhagic complications was each 2.6% and was not correlated with the quality of anticoagulation. Quality of anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol, concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. Conclusion: The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKA dose, and the use of prescription assistance software.
文摘Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.
文摘Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.
基金Hainan Clinical Medical CenterMajor Science and Technology Project of Hainan Province(No.ZDKJ2021037)+3 种基金National Natural Science Foundation of China(No.81960283,82072880)Funded by the Innovation Center of Academician Team of Hainan ProvinceKey R&D Project of Hainan Province(No.ZDYF2022SHFZ311)Hainan Science and Technology Program(Clinical Medical Research Center:LCYX202203,LCYX202102)。
文摘Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of estrogen pre-treatment in antagonist prorocol were searched in PubMed,Web of Science,China National Knowledge Infrastructure,Wanfang Database.R software was used for meta-analysis.Results:Seven RCTs and two retrospective studies were included.In order to explore the source of heterogeneity,subgroup analysis was used,which was mainly conducted according to the ovarian response of the included population,which were divided into low responders,non-low responders and mixed responders.In the study about gonadotropin hormone(Gn)days,patients were divided into wash-out subgroup and non-wash-out subgroup according to drug use-pattern.Meta-results showed that the number of Gn days increased significantly in the non-wash-out subgroup(WMD=1.07,95%CI[0.83;1.31],I2=66%).The number of Gn days in the wash-out subgroup were not affected(WMD=-0.12,95%CI[-0.45;0.21],I2=0%).In the low-response subgroup,the number of oocytes retrieved(WMD=0.46,95%CI[-0.23;1.16],I2=81%),the fresh cycle clinical pregnancy rate(RR=0.77,95%CI[0.55;1.06],I2=73%)and the cycle cancellation rate(RR=0.80,95%CI[0.40;1.61],I2=83%)were not significantly changed with estrogen pre-treatment.In the non-low-response subgroup,the number of oocytes obtained(WMD=0.21,95%CI[-0.69;1.11],I2=2%),fresh cycle clinical pregnancy rate(RR=0.94,95%CI[0.77;1.14],I2=41%),live birth rate(RR=0.82,95%CI[0.62;1.08],I2=0%)and cycle cancellation rate(RR=0.89,95%CI[0.54;1.47],I2=2%)were not significantly changed with estrogen pre-treatment.Conclusions:Estrogen pre-treatment(with non-wash-out period)in antagonist protocol increases Gn days,dose not improve IVF outcomes in non-low responders and low responders.
文摘BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.
基金supported by the 2020-Innovation Project-Yi An,and Applied basic research plan of Hebei province-key basic research projects(17967502D).
文摘Aflatoxin is a strong carcinogenic and toxic fungal toxin produced by Aspergillus flavus and other Aspergillus species,and can seriously threaten the health of consumers,thus becoming a global concern.Corn,as an important oil and economic crop,is highly susceptible contaminated by aflatoxin.In this study,antagonistic bacteria with strong inhibitory effect on aflatoxin were screened to provide support for the treatment aflatoxin contamination control in corn.Ten strains which have strong antagonistic effects against A.flavus were isolated from healthy corn from different corn producing areas in China.Among them,the antagonistic bacteria JTFM1001 through corn kernels in vivo and field experiment,the inhibition effect of aflatoxin contamination reached above 70%and 55%,respectively.And the strain was identified as Bacillus subtilis based on its morphological,physiological and biochemical characteristics and phylogenetic analysis of 16S rDNA.In addition,our data showed that it can colonize in the rhizosphere and survive for a long time,forming the dominant flora,with broad application prospect.Finally,we were surprised to find that the antibacterial metabolites secreted by the antagonistic bacteria was one of the mechanisms of its inhibition of A.flavus and aflatoxin.This will provide us with new ideas and perspectives on the effective prevention and control of aflatoxin contamination in corn and corn oil.
基金University Grants Commission, New Delhi,India for providing UGC Fellowship[UGC letter DON F.19-33/2006(CU)]Department of Science & Technology,Ministry of Science & Technology, Government of India for awarding "Young Scientist Project Award"(FT/SR-L-111/2006)
文摘Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.
文摘AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.
文摘BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.
基金Supported by National Natural Science Funds of China,No.81102784/H2803the key project in scientific research from ministry of education,No.212032Liaoning Innovative Research Team in University,No.LT2013022
文摘AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.
文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.
基金This work was supported by the National Natural Science Foundation of China (Nos.81471455,81100418).
文摘Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.
基金supported in part by the National Natural Sci-ence Foundation of China(81472284 and 81672699)Shanghai Pujiang Program(16PJD004)
文摘Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
基金Supported by National Natural Science Foundation of China,No. 30901431
文摘AIM: To study the efficacy of marrow mesenchymal stem cells (MSCs) transplantation combined with interleukin-1 receptor antagonist (IL-1Ra) for acute liver failure (ALF). METHODS: Chinese experimental miniature swine were randomly divided into four groups (n = 7), and all animals were given D-galactosamine (D-gal) to induce ALF. Group A animals were then injected with 40 mL saline via the portal vein 24 h after D-gal induction;Group B animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h, 2 d and 4 d after D-gal induction; Group C received approximately 1 × 108 green fluorescence protein (GFP)-labeled MSCs (GFP-MSCs) suspended in 40 mL normal saline via the portal vein 24 h after D-gal induction; Group D animals were injected with 2 mg/kg IL-1Ra via the ear vein 18 h after D-gal induction, MSCs transplantation was then carried out at 24 h after D-gal induction, and finally 2 mg/kg IL-1Ra was injected via the ear vein 1 d and 3 d after surgery as before. Liver function, serum inflammatory parameters and pathological changes were measured and the fate of MSCs was determined.RESULTS: The optimal efficiency of transfection (97%) was achieved at an multiplicity of infection of 80, as observed by fluorescence microscopy and flow cytometry (FCM). Over 90% of GFP-MSCs were identified as CD44+ CD90+ CD45-MSCs by FCM, which indicated that most GFP-MSCs retained MSCs characteristics. Biochemical assays, the levels of serum inflammatory parameters and histological results in Group D all showed a significant improvement in liver injury compared with the other groups (P < 0.05). The number of GFP-MSCs in Group D was also greater than that in Group B, and the long-term cell proliferation rate was also better in Group D than in the other groups.CONCLUSION: MSCs transplantation is useful in ALF, IL-1Ra plays an important role in alleviating the inflammatory condition, and combination therapy with MSCs transplantation and IL-1Ra is a promising treatment for ALF.
基金the National Natural Science Foundation of China(No.81401177)Guangdong Province Natural Science Foundation(No.2015A030313286)Milstein Medical Asian American Partnership Foundation Fellowship Award in Reproductive Medicine,Nanfang Hospital High-level Project Matching Funds(No.G2014005).
文摘This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.
基金supported by the Faculty of Health Sciences,Universiti Teknologi MARA,Puncak Alam Campus,Selangor and LESTARI grant(600-IRMI/MYRA 5/3/LESTARI(16/2016)
文摘Objective: To investigate the effects of Andrographis paniculata(Burm.f.) Wall. Ex Nees(A. paniculata) on expressions and activities of catalase, superoxide dismutase and alkylhydroperoxide reductase C in Staphylococcus aureus(S. aureus) with respect to its survival in vitro. Methods: Antioxidative property of methanolic leaves extract of A. paniculata(0.06 mg/m L). Minimum inhibitory concentration(MIC) was determined by its ability to reduce hydrogen peroxide(H_2O_2) toxicity against S. aureus ATCC 25923(3.8×10~8 cfu/m L). Effects of the extract on expressions of kat A(encoding catalase), sod A and sod M [encoding superoxide dismutases(SODs)], and ahp C [encoding alkylhydroperoxide reductase C(AhpC)] in S. aureuswere determined by RT-q PCR and corresponding enzyme activity assays were performed. Nitroblue tetrazolium reduction(NBT) assay was performed to determine effects of the extract on intracellular and extracellular levels of O_2-in S. aureus. Results: Cells challenged with 7.5 mmol/L H_2O_2 showed 0% survival in 30 min whereas 25% survived after treatment with the extract and H_2O_2. Cells that were treated with the extract alone had 43% survival in the same exposure period. Expressions of sod A and sod M genes in extract-treated cells were lowered 0.8-fold and 0.7-fold, respectively with decrease in total SOD activity of 26.8 U compared to untreated cells, 32.4 U(P<0.05). In contrast, extract-treated S. aureus cells showed 3.3-fold increase in kat A expression with corresponding increase in catalase activity of 1.828 U compared to untreated cells which was 1.248 U,(P<0.05). More profoundly, ahp C expression was increased 61-fold in extract-treated cells,(P<0.05) with corresponding increase in Ahp C activity of 0.018 U compared to untreated cells, 0.012U,(P<0.05). Extract-treated cells had significantly lower intra-and extracellular O_2-levels with absorbance readings(A_(575nm)) of 0.340 and 0.524 compared to untreated cells which were 0.516 and 0.928(P<0.05), respectively. Conclusions: Taken together these results suggest that the low MIC of A. paniculatamethanolic leaves extract(0.06 mg/m L) reduce H_2O_2 toxicity and more importantly, was in itself effectively inhibitory against S. aureus. Further, our observations suggest that a probable mode of its inhibitory mechanism against S. aureus is by reducing total SOD activity through downregulation of sod A and sod M expressions.
基金supported by Foundation for Innovative Research Groups of National Natural Science Foundation of China(NSFC)(61321002)National Science Fund for Distinguished Young Scholars(60925011)+2 种基金Projects of Major International(Regional)Joint Research Program NSFC(61120106010)Beijing Education Committee Cooperation Building Foundation Project,Program for Changjiang Scholars and Innovative Research Team in University(IRT1208)Chang Jiang Scholars Program and National Natural Science Foundation of China(61203078)
文摘At present, the studies on multi-team antagonistic games(MTAGs) are still in the early stage, because this complicated problem involves not only incompleteness of information and conflict of interests, but also selection of antagonistic targets.Therefore, based on the previous researches, a new framework is proposed in this paper, which is dynamic multi-team antagonistic games with incomplete information(DMTAGII) model.For this model, the corresponding concept of perfect Bayesian Nash equilibrium(PBNE) is established and the existence of PBNE is also proved. Besides, an interactive iteration algorithm is introduced according to the idea of the best response for solving the equilibrium. Then, the scenario of multiple unmanned aerial vehicles(UAVs) against multiple military targets is studied to solve the problems of tactical decision making based on the DMTAGII model. In the process of modeling, the specific expressions of strategy, status and payoff functions of the games are considered, and the strategy is coded to match the structure of genetic algorithm so that the PBNE can be solved by combining the genetic algorithm and the interactive iteration algorithm.Finally, through the simulation the feasibility and effectiveness of the DMTAGII model are verified. Meanwhile, the calculated equilibrium strategies are also found to be realistic, which can provide certain references for improving the autonomous ability of UAV systems.
文摘Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric cancers.To date,16 cases of PIVKA-Ⅱ-producing gastric cancer have been reported,2 of which were reported by us and all of which were identified in Japan.There are no symptoms specific to PIVKA-Ⅱ-producing gastric cancer,and the representative clinical symptoms are general fatigue,appetite loss,and upper abdominal pain.Serum alpha-feto-protein(AFP)levels are also increased in almost allcases.Liver metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is ob-served in approximately 20% of cases.Differential diagnosis between metastatic liver tumor and HCC is often difficult.Grossly,almost all cases appear as advanced gastric cancer.Histologically,a hepatoid pattern is observed in many cases,in addition to a moderately to poorly differentiated adenocarcinoma component.The production of PIVKA-Ⅱ and AFP is usually confirmed using immunohistochemical staining.Treatment and prognosis largely depends on the existence of liver meta-stasis,and the prognosis of patients with liver metas-tasis is very poor.PIVKA-Ⅱ may be produced during the hepatocellular metaplasia of the tumor cells.
基金Supported by the National Natural Science Foundation of China(No.31670355)the Natural Science Foundation for Distinguished Young Scholars of Shandong Province(No.JQ201712)the Open Fund of Key Laboratory of Experimental Marine Biology,Chinese Academy of Sciences(No.KF2017NO4)
文摘To explore the metabolic responses of marine-derived Trichoderma fungi to environmental stresses, the survivability, metabolism, and antagonism of ten marine isolates have been examined. Their survival in both freshwater and seawater indicates them to be facultative marine fungi, but they are more adaptable to marine environment. Most of them feature strain-specific and positive metabolic responses to seawater, which also usually result in the higher proportions of heteroatom-bearing and unsaturated units in mycelial constituents. Seawater factors can promote many strains to produce bioactive metabolites, including plant pathogen- and marine phytoplankton-inhibitory and marine animal-toxic ones, but the eff ects of NaCl are often weak or negative. The inhibition of marine phytoplankton corresponds to the intracellular accumulation of heteroatom-bearing and unsaturated units under seawater condition, and the varied toxicities to marine animals further signify the divergences of lipophilic exudates under diff erent conditions. The results may contribute to further understanding and mining the structural diversity and biological activity of secondary metabolites from marine-derived Trichoderma fungi.
文摘Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.
